Strategies for inclusion of growth factors into 3D printed bone grafts

2021 ◽  
Author(s):  
Alessia Longoni ◽  
Jun Li ◽  
Gabriella C.J. Lindberg ◽  
Jelena Rnjak-Kovacina ◽  
Lyn M. Wise ◽  
...  

Abstract There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties. The incorporation of growth factors (GFs), which are the natural orchestrators of the physiological healing process, into 3D printed bone grafts, represents a promising strategy to achieve the bioactivity required to enhance bone regeneration. In this review, the possible strategies used to incorporate GFs to 3D printed constructs are presented with a specific focus on bone regeneration. In particular, the strengths and limitations of different methods, such as physical and chemical cross-linking, which are currently used to incorporate GFs to the engineered constructs are critically reviewed. Different strategies used to present one or more GFs to achieve simultaneous angiogenesis and vasculogenesis for enhanced bone regeneration are also covered in this review. In addition, the possibility of combining several manufacturing approaches to fabricate hybrid constructs, which better mimic the complexity of biological niches, is presented. Finally, the clinical relevance of these approaches and the future steps that should be taken are discussed.

2020 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Erica Floreani ◽  
Malavika H Nambiar ◽  
...  

AbstractThorough preclinical evaluation of novel biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of biomaterials using collagen and BMP-2 as test materials. Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of biomaterials.This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of biomaterials.


2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
R. V. Deev ◽  
A. Y. Drobyshev ◽  
I. Y. Bozo ◽  
A. A. Isaev

Bone grafts are medical devices that are in high demand in clinical practice for substitution of bone defects and recovery of atrophic bone regions. Based on the analysis of the modern groups of bone grafts, the particularities of their composition, the mechanisms of their biological effects, and their therapeutic indications, applicable classification was proposed that separates the bone substitutes into “ordinary” and “activated.” The main differential criterion is the presence of biologically active components in the material that are standardized by qualitative and quantitative parameters: growth factors, cells, or gene constructions encoding growth factors. The pronounced osteoinductive and (or) osteogenic properties of activated osteoplastic materials allow drawing upon their efficacy in the substitution of large bone defects.


2021 ◽  
Vol 22 (3) ◽  
pp. 1128
Author(s):  
Giulia Battafarano ◽  
Michela Rossi ◽  
Viviana De Martino ◽  
Francesco Marampon ◽  
Luca Borro ◽  
...  

Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention is needed to regenerate the tissue via the use of natural bone grafts or synthetic bone grafts. The main elements required for tissue engineering include cells, growth factors and a scaffold material to support them. Three different materials (metals, ceramics, and polymers) can be used to create a scaffold suitable for bone regeneration. Several cell types have been investigated in combination with biomaterials. In this review, we describe the options available for bone regeneration, focusing on tissue engineering strategies based on the use of different biomaterials combined with cells and growth factors.


2020 ◽  
Vol 21 (19) ◽  
pp. 7012 ◽  
Author(s):  
Tullio Genova ◽  
Ilaria Roato ◽  
Massimo Carossa ◽  
Chiara Motta ◽  
Davide Cavagnetto ◽  
...  

Reconstruction of bony defects is challenging when conventional grafting methods are used because of their intrinsic limitations (biological cost and/or biological properties). Bone regeneration techniques are rapidly evolving since the introduction of three-dimensional (3D) bioprinting. Bone tissue engineering is a branch of regenerative medicine that aims to find new solutions to treat bone defects, which can be repaired by 3D printed living tissues. Its aim is to overcome the limitations of conventional treatment options by improving osteoinduction and osteoconduction. Several techniques of bone bioprinting have been developed: inkjet, extrusion, and light-based 3D printers are nowadays available. Bioinks, i.e., the printing materials, also presented an evolution over the years. It seems that these new technologies might be extremely promising for bone regeneration. The purpose of the present review is to give a comprehensive summary of the past, the present, and future developments of bone bioprinting and bioinks, focusing the attention on crucial aspects of bone bioprinting such as selecting cell sources and attaining a viable vascularization within the newly printed bone. The main bioprinters currently available on the market and their characteristics have been taken into consideration, as well.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ayesha Suleman ◽  
Pierre P. D. Kondiah ◽  
Mostafa Mabrouk ◽  
Yahya E. Choonara

Osteosarcoma is a malignant bone neoplasm prevalent in adolescents. Current therapies include chemotherapy and surgery. Surgical resection of osteosarcoma induces a large bone defect which may be overcome by employing scaffolds for bone tissue engineering. This review details the polymers and bioceramics that may be used to fabricate 3D printed scaffolds for bone regeneration and the nanotechnology strategies that may be incorporated into such scaffolds. Natural polymers discussed include chitosan, alginate, collagen, gelatin, and silk fibroin. Synthetic polymers discussed include polycaprolactone, polyurethane, poly(lactic)acid and poly(vinyl) alcohol. Bioceramics that are utilized in bone regeneration such as calcium phosphate, calcium silicate and bioglass are elaborated on. Furthermore, comparison data between different types of 3D printed scaffolds for bone regeneration are presented. A discussion on Photo-responsive and magneto-responsive 3D printed scaffolds that have been fabricated for bone regeneration is included. Research concerning drug-loaded scaffolds as well as the incorporation of nanocarriers into scaffolds for bone regeneration is provided. Chemotherapy utilized in osteosarcoma therapy has severe adverse effects due to being non-selective between healthy cells and tumor cells. A possible way to overcome this is to utilize nanotechnology. Therefore, research detailing other types of nanocarriers that have the potential to be incorporated into 3D printed scaffolds for localized adjuvant therapy is presented.


2021 ◽  
Vol 22 (14) ◽  
pp. 7724
Author(s):  
Iratxe Macías ◽  
Natividad Alcorta-Sevillano ◽  
Arantza Infante ◽  
Clara I. Rodríguez

Bone damage leading to bone loss can arise from a wide range of causes, including those intrinsic to individuals such as infections or diseases with metabolic (diabetes), genetic (osteogenesis imperfecta), and/or age-related (osteoporosis) etiology, or extrinsic ones coming from external insults such as trauma or surgery. Although bone tissue has an intrinsic capacity of self-repair, large bone defects often require anabolic treatments targeting bone formation process and/or bone grafts, aiming to restore bone loss. The current bone surrogates used for clinical purposes are autologous, allogeneic, or xenogeneic bone grafts, which although effective imply a number of limitations: the need to remove bone from another location in the case of autologous transplants and the possibility of an immune rejection when using allogeneic or xenogeneic grafts. To overcome these limitations, cutting edge therapies for skeletal regeneration of bone defects are currently under extensive research with promising results; such as those boosting endogenous bone regeneration, by the stimulation of host cells, or the ones driven exogenously with scaffolds, biomolecules, and mesenchymal stem cells as key players of bone healing process.


2020 ◽  
Vol 4 (3) ◽  
pp. 153-165
Author(s):  
Vitor de Toledo Stuani ◽  
Gustavo Gonçalves do Prado Manfredi ◽  
Vitor Artur Miyahara Kondo ◽  
Pedro Yoshito Noritomi ◽  
Paulo Noronha Lisboa-Filho ◽  
...  

Gingival recessions are a highly prevalent issue that is often associated with interproximal tissue deficiency. An intervention in these scenarios is of extreme importance since these defects can lead to aesthetic, phonetic and other dental problems. Unfortunately, the treatment of advanced gingival recessions is a major challenge in periodontics because of its unpredictability. In such cases, the use of injectable fillings, connective tissue grafts or bone grafts for vertical regeneration in interproximal area presents limited results. Considering that, this special report reviewed the possible use of additively manufactured scaffolds as a therapeutic option. A 3D-printed personalized therapy is expected to simplify the regeneration of interproximal area, enabling bone regeneration, new papilla formation and root coverage.


2014 ◽  
Vol 2 (43) ◽  
pp. 7583-7595 ◽  
Author(s):  
Jianhua Zhang ◽  
Shichang Zhao ◽  
Min Zhu ◽  
Yufang Zhu ◽  
Yadong Zhang ◽  
...  

The 3D-printed Fe3O4/MBG/PCL scaffolds with potential multifunctionality would be promising for use in the treatment and regeneration of large bone defects after tumor resection.


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